Neuropathic pain management is a major unmet clinical need. Classically used medications (opioids and non-opioids/NSAIDs) have major side effects associated with their use, and many individuals do not respond to any medications. Neuropathic pain drugs with novel mechanisms of action are being sought as alternatives; however, the only novel FDA-approved drugs, which target calcium channels, have serious limitations to their general use. Neurotensin (NT) and its fully active fragment NT(8-13) possess dramatic activity against neuropathic pain when dosed centrally; however, activity is not seen with systemic administration. JT Pharmaceuticals has engineered NT(8-13) derivatives that exhibit potent analgesic activity when dosed IV and, at high concentrations, orally. The compounds are NT-receptor agonists, thus operating by a novel mechanism so they are expected not to have the limitations of current analgesics. In previous work in this program, the NT(8-13) derivative HPI201 was selected as the lead for advancement, and a wide variety of IND-enabling activities were performed. This constituted the Phase I portion of this program. In this Direct Phase II SBIR application to advance the program, we hypothesize that completion of three Specific Aims will enable HPI201 to be advanced to clinical trials. In Specific Aim 1, the pharmacokinetic/pharmacodynamics properties of HPI201 will be fully characterized. The PK/PD data are crucial for developing the study designs for preclinical toxicity and safety evaluations in animals, prediction of effective human dose, and ultimately design of clinical trials. In Specific Aim 2, activities necessary for preparation and submission of an IND, most notably 28-day toxicity studies in rats and dogs, will be completed. The goals of Specific Aim 3 will be preparation and submission of the IND to enable initiation of clinical trials. Completion o Specific Aim 1 will be performed at JT Pharma in collaboration with the PI's long-term collaborator, Dr. Craig Beeson, at the Medical University of South Carolina, Specific Aim 2 will be outsourced to a highly reputable contract lab, and Specific Aim 3 will be performed at JT Pharma with the aid of consultants as necessary.